Diagnostic Value of High-Mobility Group Box 1 (HMGB1) Protein in Acute and Perforated Appendicitis

Aim: Acute appendicitis is the most common cause of abdominal surgical emergencies. Early diagnosis of appendicitis can reduce perforation and mortality rate. High-mobility group box 1 (HMGB1) protein has been identified as a pro-inflammatory factor and its elevated serum levels have been noted in different diseases. So, the aim of this study was to determine the serum levels of HMGB1 in patients with acute and perforated appendicitis in compare to normal appendix. Material and methods: For this purpose, serum samples were obtained from 81 patients with primary criteria-based appendicitis 6 hr before and 72 hr after appendectomy, in which serum levels of HMGB1 were analyzed by enzyme-linked immunosorbent assay. Results: The levels of HMGB1 in patients with perforated appendicitis were significantly (p =.045) higher than in patients with acute appendicitis and normal appendix (p =.001) before appendectomy. Serum levels of HMGB1 were increased 72 hr after appendectomy in all the groups (p =.03) compared with the serum levels before appendectomy. Conclusions: Since the serum levels of HMGB1 in patients with acute and perforated appendicitis were higher than in patients with normal appendix, these findings could be useful to develop a new biomarker along with other laboratory tests for accurate diagnosis of patients with appendicitis.     

Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia.

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.     

Bariatric Surgery Promising in Migraine Control: a Controlled Trial on Weight Loss and Its Effect on Migraine Headache

Introduction

There is evidence that substantial weight loss through bariatric surgery (BS) may result in short-term improvement of migraine severity. However, it still remains to be seen whether smaller amounts of weight loss have a similar effect on migraine headache. This study has been designed to compare the effects of weight reduction through BS and non-surgical modifications.

Materials and Methods

Migraine characteristics were assessed at 1 month before (T0), 1 month (T1), and 6 months (T2) after BS (vertical sleeve gastrectomy (VSG) (n = 25) or behavioral therapy (BT) (n = 26) in obese women (aged 18–60 years) with migraine headache. Migraine was diagnosed using the International Classification of Headache Disorders (ICHDIIβ) criteria.

Results

There was significant reduction in the visual analog scale (VAS) from the baseline to T1 and T2 in both groups. The number of migraine-free days showed a significant increase within each group (p < 0.001). The BS group had a significant reduction in attack duration (p < 0.001) while there were no changes observed within the BT group. Following the adjustment of ANCOVA models for baseline values of migraine characteristics, age, changes in weight, BMI, body fat, and fat-free mass from T0 to T2, the BS group showed statistically significant lower VAS and duration of migraine attacks and a significantly higher number of migraine-free days than the BT group at T1 and T2 (p ≤ 0.028).

Conclusion

Our results indicated that far before significant weight reduction after BS (VSG), there was marked alleviation in the severity and duration of migraine and a significant increase in the number of migraine-free days in obese female migraineurs. However, the effects in the BT group were not comparable with the effects in the BS group.

     

Surprise! HSC are aberrant in chronic lymphocytic leukemia

In this issue of Cancer Cell, Kikushige et?al. report the surprising finding that, in human chronic lymphocytic leukemia (CLL), hematopoietic stem cells (HSC) aberrantly generate clonal B cells with CLL-like phenotypes, which implicate HSC in the pathogenesis of this mature lymphoid malignancy and has major implications for CLL therapies.     

Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by [... formula ...] rather than by phosphoranes

Prior evidence supporting the direct observation of phosphorane intermediates in enzymatic phosphoryl transfer reactions was based on the interpretation of electron density corresponding to trigonal species bridging the donor and acceptor atoms. Close examination of the crystalline state of β-phosphoglucomutase, the archetypal phosphorane intermediate-containing enzyme, reveals that the trigonal species is not PO3-, but is MgF3- (trifluoromagnesate). Although MgF3- complexes are transition state analogues rather than phosphoryl group transfer reaction intermediates, the presence of fluorine nuclei in near-transition state conformations offers new opportunities to explore the nature of the interactions, in particular the independent measures of local electrostatic and hydrogen-bonding distributions using F19 NMR. Measurements on three β-PGM-MgF3--sugar phosphate complexes show a remarkable relationship between NMR chemical shifts, primary isotope shifts, NOEs, cross hydrogen bond F ? H-N scalar couplings, and the atomic positions determined from the high-resolution crystal structure of the β-PGM-MgF3--G6P complex. The measurements provide independent validation of the structural and isoelectronic MgF3- model of near-transition state conformations.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:B-cell signaling networks reveal a negative prognostic human lymphoma cell subset that emerges during tumor progression

Human tumors contain populations of both cancerous and host immune cells whose malignant signaling interactions may define each patient''s disease trajectory. We used multiplexed phospho-flow cytometry to profile single cells within human follicular lymphoma tumors and discovered a subpopulation of lymphoma cells with impaired B cell antigen receptor (BCR) signaling. The abundance of BCR-insensitive cells in each tumor negatively correlated with overall patient survival. These lymphoma negative prognostic (LNP) cells increased as tumors relapsed following chemotherapy. Loss of antigen receptor expression did not explain the absence of BCR signaling in LNP tumor cells, and other signaling responses were intact in these cells. Furthermore, BCR signaling responses could be reactivated in LNP cells, indicating that BCR signaling is not missing but rather specifically suppressed. LNP cells were also associated with changes to signaling interactions in the tumor microenvironment. Lower IL-7 signaling in tumor infiltrating T cells was observed in tumors with high LNP cell counts. The strength of signaling through T cell mediator of B cell function CD40 also stratified patient survival, particularly for those whose tumors contained few LNP cells. Thus, analysis of cell–cell interactions in heterogeneous primary tumors using signaling network profiles can identify and mechanistically define new populations of rare and clinically significant cells. Both the existence of these LNP cells and their aberrant signaling profiles provide targets for new therapies for follicular lymphoma.     

Genetic and serological markers to identify phenotypic subgroups in a Dutch Crohn’s disease population

BACKGROUND AND AIMS: Both genetic and microbial factors seem to play a pivotal role in the aetiopathogenesis of Crohn's disease. The CARD15 frameshift mutation might link host genetic factors and the indigenous microbial flora, since CARD15 expression is stimulated by peptidoglycan, thereby activating NF-kappaB. It is hypothesised that CARD15 mutation carriers have defective anti-microbial reactions, resulting in more penetrating lesions and antibody responses, which are now being used as highly specific markers for Crohn's disease. The serological marker anti-Saccharomyces cerevisiae antibody directed against cell wall oligomannosidic epitopes has high specificity for Crohn's disease. Perinuclear anti-neutrophil cytoplasmic antibodies have been found in a subgroup of Crohn's disease patients, mostly with colonic involvement. METHODS: We investigated the incidence of two CARD15 mutations (3020insC and 2722G>C), anti-S. cerevisiae antibody, and perinuclear anti-neutrophil cytoplasmic antibody in 108 (73F/35M) patients with Crohn's disease with a mean duration of disease since diagnosis of 16 (1-41) years in relation to their phenotype, according to the Vienna classification. RESULTS: The prevalence of CARD15 frameshift mutation was 21%. Of all patients, 62% were anti-S. cerevisiae antibody positive, and 9% had perinuclear anti-neutrophil cytoplasmic antibodies. The prevalence of both anti-S. cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies was higher in the mutation carriers compared to non-carriers. Remarkably, all patients with a CARD15 mutation and positive anti-S. cerevisiae antibody had ileal disease. Carriership of the mutation was significantly associated with penetrating behaviour of the disease and weakly associated with stricturing behaviour. Furthermore, anti-S. cerevisiae antibody was associated with ileal disease involvement. Finally, most perinuclear anti-neutrophil cytoplasmic antibody positive patients showed ulcerative-like behaviour of disease (by means of colonic localisation). CONCLUSIONS: Genetic and serologic markers might be useful in defining patient subgroups. This may result in a more accurate prediction of disease behaviour, prognosis and therapeutic approach.